Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A girl with partial lipodystrophy is described presenting with muscle weakness and developmental delay several years before lipoatrophy became apparent. The patient subsequently developed epilepsy, fatty liver, secondary amenorrhoea, hirsutism, insulin-resistant diabetes mellitus, hyperlipidaemia, and hypothyroidism. She remains weak with poor exercise tolerance. This case illustrates an atypical presentation of the Barraquer-Simon syndrome.
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PMID:Partial lipodystrophy presenting with myopathy. 1007 99

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and underpins the strong association between obesity and diabetes. Paradoxically, the metabolic consequences of having 'too much' fat (obesity) are remarkably similar to those of having 'too little' fat (lipodystrophy): a finding that has generated considerable interest in a rare disease. In both cases, excess energy accumulates as lipid in ectopic sites such as the liver (fatty liver) and skeletal muscle, where it plays a central role in the pathogenesis of insulin resistance, dyslipidemia and type 2 diabetes. Human lipodystrophies are characterised by a total or partial deficiency of body fat, and may be inherited or acquired in origin. Genetically engineered mice with generalised lipodystrophy manifest many of the features of the human disorder, including hyperphagia, fatty liver, hypertriglyceridaemia, insulin resistance and type 2 diabetes, providing a useful tractable model of the human disorder. Partial lipodystrophy, which causes similar, albeit milder, metabolic problems in humans has been more difficult to mimic in the mouse. This review discusses key translational studies in mice with generalised lipodystrophy, including fat transplantation and the use of recombinant leptin replacement therapy. These studies have been instrumental in advancing our understanding of the underlying molecular pathogenesis of ectopic lipid accumulation and insulin resistance, and have prompted the initiation and subsequent adoption of leptin replacement therapy in human lipodystrophies. This review also considers the possible reasons for the apparent difficulties in generating mouse models of partial lipodystrophy, such as interspecies differences in the distribution of fat depots and the apparent lack of sexual dimorphism in fat mass and distribution in mice compared with the dramatic differences present in adult humans.
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PMID:Mouse models of inherited lipodystrophy. 1989 86

Acquired partial lipodystrophy (APL) is a rare disorder, mainly characterized by progressive loss of subcutaneous fatty tissue, starting from the face and spreading to the upper part of the body. The etiology of APL is unknown. It may be caused by mutations in the lamin B 2 (LMNB2) gene on 19p13.3. We present a Chinese patient who hadAPL for 12 years, which initially affected her face. She also suffered from marked fatty liver and a mild metabolic disorder. We identified a heterozygous T to C transition in exon 5 of the LMNB2 gene (c.694T>C), and, consequently, tyrosine for histidine (p.Y232H). However, these features and the mutation were absent in her parents. The p.Y232H has not been described previously. We provide clinical data to the genotype-phenotype discussion and further expanded the number of LMNB2 mutations.
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PMID:A Chinese patient with acquired partial lipodystrophy caused by a novel mutation with LMNB2 gene. 2276 73

Lipodystrophies are an immense group of genetic or acquired metabolic disorders that are characterized by varying degrees of body fat loss and in some instances localized accumulation of subcutaneous fat. Lipodystrophies are often tightly linked with profound metabolic complications; this strong bond emphasizes and reinforces the significance of adipose tissue as a dynamic endocrine organ. The extent of fat loss determines the severity of associated metabolic complications such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis. The lipodystrophies can be divided into generalized, partial or local, depending on the degree and locality of the observable fat loss; moreover, the generalized and partial divisions can be partitioned further into inherited or acquired forms. The major genetic factors in the generalized forms of the lipodystrophies, particularly Congenital generalized lipodystrophy (CGL)-Berardinelli-Seip syndrome, are the AGPAT2, BSCL2, caveolin 1 (CAV1) and polymerase-I-and-transcriptrelease factor (PTRF) genes. In the acquired forms, genes such as LMNA, PPARG, CIDEC (cell-death-inducing DNA fragmentation factor a-like effector c) and PLIN1 are heavily involved in familial partial lipodystrophy (FPLD) type 2 (also known as the Dunnigan-Variety) and WRN along with RECQL5 in Werner Syndrome (WS). Autoimmune causes are particularly noted in acquired partial lipodystrophy (APL)-Barraquer-Simons syndrome and in AGL-Lawrence syndrome; panniculitis has been shown to have a substantial role in the former as well as in other forms of localized lipodystrophies. Patients with human immunodeficiency virus (HIV) exposed to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) (for example, zidovudine and stavudine) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) (for example, efavirenz) while undergoing Highly Active Antiretroviral Therapy (HAART) have led to the current most-prevalent form of the lipodystrophies: lipodystrophy in HIV-infected patients (LD-HIV) and HAART-associated lipodystrophy syndrome (HALS).
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PMID:Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies. 2415 69

Partial lipodystrophy (PD), a condition similar to metabolic syndrome without obesity, is one of the late complications of hematopoietic stem cell transplantation (HSCT) performed during childhood. We aimed to investigate the prevalence and risk factors of PD. A cross-sectional survey was performed in a children's hospital, targeting patients treated for a malignancy or hematological disorder, and who were disease-free for > 24 mo. PD was defined as gluteal lipoatrophy and lipohypertrophy of the cheeks or neck associated with diabetes and/or fatty liver disease. In total, 65 patients were enrolled. Six patients (9.2%) were judged to have PD, all of whom had received 10-14 Gy total body irradiation. Compared with the patients without PD, patients with PD were older at investigation (P < 0.01), had a longer elapsed time following HSCT (P < 0.01), had more frequent disease recurrence (P < 0.05), and were more likely to have undergone multiple HSCT (P < 0.05). In addition, they had higher blood pressure and showed higher levels of low-density lipoprotein-cholesterol and triglycerides, whereas their adiponectin levels were significantly lower. In conclusion, a large number of patients developed PD following HSCT, with unfavorable metabolic profiles at a later age, especially when they experienced a complex disease course.
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PMID:Partial lipodystrophy in patients who have undergone hematopoietic stem cell transplantation during childhood: an institutional cross-sectional survey. 2845 62

The liver executes 500+ functions, such as protein synthesis, xenobiotic metabolism, bile production, and metabolism of carbohydrates/fats/proteins. Such functions can be severely degraded by drug-induced liver injury, nonalcoholic fatty liver disease, hepatitis B and viral infections, and hepatocellular carcinoma. These liver diseases, which represent a significant global health burden, are the subject of novel drug discovery by the pharmaceutical industry via the use of in vitro models of the human liver, given significant species-specific differences in disease profiles and drug outcomes. Isolated primary human hepatocytes (PHHs) are a physiologically relevant cell source to construct such models; however, these cells display a rapid decline in the phenotypic function within conventional 2-dimensional monocultures. To address such a limitation, several engineered platforms have been developed such as high-throughput cellular microarrays, micropatterned cocultures, self-assembled spheroids, bioprinted tissues, and perfusion devices; many of these platforms are being used to coculture PHHs with liver nonparenchymal cells to model complex cell cross talk in liver pathophysiology. In this perspective, we focus on the utility of representative platforms for mimicking key features of liver dysfunction in the context of chronic liver diseases and liver cancer. We further discuss pending issues that will need to be addressed in this field moving forward. Collectively, these in vitro liver disease models are being increasingly applied toward the development of new therapeutics that display an optimal balance of safety and efficacy, with a focus on expediting development, reducing high costs, and preventing harm to patients.
APL Bioeng 2019 Dec
PMID:Emerging trends in modeling human liver disease in vitro. 3189 56